Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm with a substantial risk of thromboembolic events (TEs), which contribute to morbidity and mortality. Traditional thrombotic risk stratification primarily considers age and thrombosis history, yet these parameters alone do not capture the complexity of thrombotic risk. Growing evidence highlights the role of additional factors influencing the risk of TEs, underscoring the need for a more comprehensive approach to patient stratification. This paper reviews the current understanding of thromboembolic risk factors in PV and provides the rationale, methodology, and expected contributions of the PROSPERO study, a prospective, multicenter study designed to improve thrombotic risk assessment in patients with high-risk PV. By examining established (advanced age, prior TEs, cardiovascular comorbidities) and emerging thromboembolic risk factors, including specific hematologic parameters, the study aims to emphasize their impact and potential synergistic interactions on thrombotic risk. This review also evaluates the efficacy and limitations of current therapies, such as hydroxyurea (HU), interferons, and ruxolitinib, in preventing TEs, and further underscores the need for comprehensive predictive models to guide individualized management strategies. The PROSPERO study focuses on high-risk PV patients who experienced at least one prior TE and receive either HU or ruxolitinib, aiming to identify predictive factors for TEs and their individual and combined contributions to thrombotic risk by collecting longitudinal data on clinical, laboratory, and treatment-related parameters. PROSPERO aims to identify and validate new variables that can inform the development of precise, integrated prediction models. The findings are expected to enable tailored treatment approaches, ultimately reducing TE recurrence in high-risk PV populations.